Elucidation of the mechanism of insulin's stimulatory action on glucose metabolism and its perturbation in obesity and with altered dietary carbohydrate and fat content has been undertaken using the isolated rat adipose cell as a model. Mathematical modeling of the complex kinetics of insulin binding is in progress. A specific D-glucose-inhibitable 3-H-cytochalasin B binding assay for quantitating the number of glucose transport systems in subcellular membrane fractions has been developed and a large intracellular pool of glucose transport systems identified in association with the Golgi fraction. Detailed kinetic, reversal, and insulin concentration experiments further establish that insulin appears to stimulate glucose transport by triggering a rapid and reversible translocation of glucose transport systems from this intracellular pool to the plasma membrane. Studies in enlarged adipose cells from obese rats further suggest that increased basal glucose transport and the markedly diminished transport response to insulin are accounted for by an insulin-like redistribution of transport systems even in the basal state. An examination of the quantitative relationship between insulin binding and the stimulation of glucose transport is also in progress.